CD11c-expressing Ly6C<sup>+</sup>CCR2<sup>+</sup> monocytes constitute a reservoir for efficient <i>Leishmania</i> proliferation and cell-to-cell transmission

by Sandrina Heyde, Lars Philipsen, Pauline Formaglio, Yan Fu, Iris Baars, Guido Höbbel, Corinna Kleinholz, Elena A. Seiß, Juliane Stettin, Patricia Gintschel, Anne Dudeck, Philippe Bousso, Burkhart Schraven, Andreas J. Müller

The virulence of intracellular pathogens such as Leishmania major (L. major) relies largely on their ability to undergo cycles of replication within phagocytes, release, and uptake into new host cells. While all these steps are critical for successful establishment of infection, neither the cellular niche of efficient proliferation, nor the spread to new host cells have been characterized in vivo. Here, using a biosensor for measuring pathogen proliferation in the living tissue, we found that monocyte-derived Ly6C+CCR2+ phagocytes expressing CD11c constituted the main cell type harboring rapidly proliferating L. major in the ongoing infection. Synchronization of host cell recruitment and intravital 2-photon imaging showed that these high proliferating parasites preferentially underwent cell-to-cell spread. However, newly recruited host cells were infected irrespectively of their cell type or maturation state. We propose that among these cells, CD11c-expressing monocytes are most permissive for pathogen proliferation, and thus mainly fuel the cycle of intracellular proliferation and cell-to-cell transfer during the acute infection. Thus, besides the well-described function for priming and activating T cell effector functions against L. major, CD11c-expressing monocyte-derived cells provide a reservoir for rapidly proliferating parasites that disseminate at the site of infection.

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